The liver has a vital role in the metabolism of intracellular and extracellular materials and is a biological organ where enzyme reactions and energy metabolism occur continuously. Currently in Korea, hepatitis, liver cirrhosis, and liver cancer along with circulatory diseases account for the highest percentage among the chronic diseases, and they also belong to leading causes of death due to diseases. In particular, since Korea has a relatively high percentage of drinking population compared to those in developed countries and since heavy alcohol drinking is associated with a high risk of liver damage, Korean people are highly concerned about the seriousness of the liver-related diseases. Continuous damage in liver tissue due to viral infection or drinking can lead to liver cirrhosis or liver cancer. Considering the physiological characteristics and importance of liver tissue, it is very important to prevent and treat liver diseases. Accordingly, there is a need for the development of a pharmaceutical composition for preventing and treating liver-related diseases that can reduce damage in liver tissue and can be ultimately applicable to the treatment thereof
Specifically, liver fibrosis is part of the physiological adaptive reaction accompanied by chronic liver diseases such as hepatitis, etc., and it refers to a state where the damaged liver tissue is transformed into fibrous tissue such as collagen instead of being recovered into normal liver cells. Although liver fibrosis is a physiological adaptive reaction that occurs in the course of recovering damaged tissue, the deterioration in liver function is inevitable because the liver tissue is replaced with fibrous tissue, which cannot perform at all the original functions of the liver, such as metabolism of in vivo materials, secretion of bile acid, etc. Since the continuous repetition of liver fibrosis can lead to liver cirrhosis and may cause death, it has been an important project to develop an appropriate therapeutic drug in the aspect of pharmaceutical drugs. However, the mechanism of liver fibrosis itself has not yet been clearly identified and thus the development of an appropriate therapeutic drug still remains to be solved.
Recently, it was discovered that transforming growth factor-beta (TGF-beta), which is a cytokine being freed from the macrophagic Kupffer cells and stellate cells in the liver, is an important mediator of liver fibrosis. Additionally, it was previously reported that the blocking of TGF-beta actions by TGF-beta antibody, antisense RNA thereof, and modifications of cellular TGF-beta receptors significantly inhibited the process of liver fibrosis. However, these studies were simply carried out at experimental levels and clinically-applicable pharmaceutical drugs are still not available.
As described above, it has been a major project to develop effective therapeutic agents for the treatment of liver fibrosis or liver cirrhosis and related studies have been carried out (Korean Patent No. 10-0949417) but the progress is still too slow.